Affinity-based design of a synthetic universal reversal agent for heparin anticoagulants

Science Translational Medicine

Volumn 6, Issue 260, 2014, Pages

  Shenoi, Rajesh A ^a   Kalathottukaren, Manu Thomas ^a   Travers, Richard J ^b   Lai, Benjamin F L ^a   Creagh, A Louise ^c   Lange, Dirk ^d   Yu, Kai ^a   Weinhart, Marie ^a   Chew, Ben H ^d   Du, Caigan ^d   Brooks, Donald E ^a,d   Carter, Cedric J ^a   Morrissey, James H ^b   Haynes, Charles A ^c   Kizhakkedathu, Jayachandran N ^a,d  

^a UNIVERSITY OF BRITISH COLUMBIA   (Canada)

^b UNIVERSITY OF ILLINOIS AT URBANA CHAMPAIGN   (United States)

^c UNIVERSITY OF BRITISH COLUMBIA   (Canada)

^d UNIVERSITY OF BRITISH COLUMBIA   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIDOTE; ENOXAPARIN; FONDAPARINUX; HEMATOLOGIC AGENT; HEPARIN; POLYMER; PROTAMINE; UNCLASSIFIED DRUG; UNIVERSAL HEPARIN REVERSAL AGENT; UNIVERSAL HEPARIN REVERSAL AGENT 1; UNIVERSAL HEPARIN REVERSAL AGENT 2; UNIVERSAL HEPARIN REVERSAL AGENT 3; UNIVERSAL HEPARIN REVERSAL AGENT 4; UNIVERSAL HEPARIN REVERSAL AGENT 5; UNIVERSAL HEPARIN REVERSAL AGENT 6; UNIVERSAL HEPARIN REVERSAL AGENT 7; UNIVERSAL HEPARIN REVERSAL AGENT 8; ANTICOAGULANT AGENT;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTICOAGULATION; ARTICLE; BLEEDING; CONTROLLED STUDY; COST EFFECTIVENESS ANALYSIS; DOSE RESPONSE; DRUG ACCUMULATION; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG DESIGN; DRUG DISTRIBUTION; DRUG DOSE ESCALATION; DRUG DOSE INCREASE; DRUG DOSE TITRATION; DRUG EFFICACY; DRUG MECHANISM; DRUG POTENCY; DRUG PROTEIN BINDING; DRUG SAFETY; DRUG STRUCTURE; DRUG SYNTHESIS; DRUG TOLERABILITY; FEMALE; HUMAN; IMMUNOGENICITY; ISOTHERMAL TITRATION CALORIMETRY; MOLECULAR WEIGHT; MOUSE; NONHUMAN; RAT; CALORIMETRY; SYNTHESIS;

ANTICOAGULANTS; CALORIMETRY; HEPARIN;

EID: 84989170252     PISSN: 19466234     EISSN: 19466242     Source Type: Journal    
DOI: 10.1182/blood-2014-05-577932     Document Type: Article

References (59)

1. N. Mackman, Triggers, targets and treatments for thrombosis. Nature 451, 914-918 (2008).
2. W. C. Francis, Clinical practice. Prophylaxis for thromboembolism in hospitalized medical patients. N. Engl. J. Med. 356, 1438-1444 (2007).
3. H. Bussey, J. L. Francis; Heparin Consensus Group, Heparin overview and issues. Pharmacotherapy 24, 103S-107S (2004).
4. J. I. Weitz, Low-molecular-weight heparins. N. Engl. J. Med. 337, 688-698 (1997).
5. B. Brenner, R. Hoffman, Emerging options in the treatment of deep vein thrombosis and pulmonary embolism. Blood Rev. 25, 215-221 (2011).
6. R. De Caterina, S. Husted, L. Wallentin, G. Agnelli, F. Bachmann, C. Baigent, J. Jespersen, S. D. Kristensen, G. Montalescot, A. Siegbahn, F. W. Verheugt, J. Weitz, Anticoagulants in heart disease: Current status and perspectives. Eur. Heart J. 28, 880-913 (2007).
7. J. Hirsh, T. E. Warkentin, R. Raschke, C. Granger, E. M. Ohman, J. E. Dalen, Heparin and lowmolecular-weight heparin: Mechanisms of action, pharmacokinetics, dosing considerations, monitoring, efficacy and safety. Chest 114, 489S-510S (1998).
8. A. Vincentelli, B. Jude, S. Bélisle, Antithrombotic therapy in cardiac surgery. Can. J. Anaesth. 53, S89-S102 (2006).
9. M. Suranyi, J. S. Chow, Review: Anticoagulation for hemodialysis. Nephrology 15, 386-392 (2010).
10. S. Alban, Adverse effects of heparin. Handb. Exp. Pharmacol. 207, 211-263 (2012).
11. D. B. Blossom, A. J. Kallen, P. R. Patel, A. Elward, L. Robinson, G. Gao, R. Langer, K. M. Perkins, J. L. Jaeger, K. M. Kurkjian, M. Jones, S. F. Schillie, N. Shehab, D. Ketterer, G. Venkataraman, T. K. Kishimoto, Z. Shriver, A. W. McMahon, K. F. Austen, S. Kozlowski, A. Srinivasan, G. Turabelidze, C. V. Gould, M. J. Arduino, R. Sasisekharan, Outbreak of adverse reactions associated with contaminated heparin. N. Engl. J. Med. 359, 2674-2684 (2008).
12. S. Schulman, R. J. Beyth, C. Kearon, M. N. Levine; American College of Chest Physicians, Hemorrhagic complications of anticoagulant and thrombolytic treatment: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 133, 257S-298S (2008).
13. M. Nagler, M. Haslauer, W. A. Wuillemin, Fondaparinux-Data on efficacy and safety in special situations. Thromb. Res. 129, 407-417 (2012).
14. Fifth Organization to Assess Strategies in Acute Ischemic Syndromes Investigators, S. Yusuf, S. R. Mehta, S. Chrolavicius, R. Afzal, J. Pogue, C. B. Granger, A. Budaj, R. J. Peters, J. P. Bassand, L. Wallentin, C. Joyner, K. A. Fox, Comparison of fondaparinux and enoxaparin in acute coronary syndromes. N. Engl. J. Med. 354, 1464-1476 (2006).
15. F. Schiele, N. Meneveau, M. F. Seronde, V. Descotes-Genon, J. Dutheil, R. Chopard, F. Ecarnot, J. P. Bassand; Reseau de Cardiologie de Franche Comte, Routine use of fondaparinux in acute coronary syndromes: A 2-year multicenter experience. Am. Heart J. 159, 190-198 (2010).
16. I. Melnikova, The anticoagulants market. Nat. Rev. Drug Discov. 8, 353-354 (2009).
17. M. A. Crowther, T. E. Warkentin, Bleeding risk and the management of bleeding complications in patients undergoing anticoagulant therapy: Focus on new anticoagulant therapy. Blood 111, 4871-4879 (2008).
18. J. Goy, M. A. Crowther, Approaches to diagnosing and managing anticoagulant-related bleeding. Semin. Thromb. Hemost. 38, 702-710 (2012).
19. M. Pai, M. A. Crowther, Neutralization of heparin activity. Handb. Exp. Pharmacol. 207, 265-277 (2012).
20. M. Nybo, J. S. Madsen, Serious anaphylactic reactions due to protamine sulfate: A systematic literature review. Basic Clin. Pharmacol. Toxicol. 103, 192-196 (2008).
21. T. Bakchoul, H. Zöllner, J. Amiral, S. Panzer, S. Selleng, T. Kohlmann, S. Brandt, M. Delcea, T. E. Warkentin, U. J. Sachs, A. Greinacher, Anti-protamine-heparin antibodies: Incidence, clinical relevance, and pathogenesis. Blood 121, 2821-2827 (2013).
22. G. Lee, I. J. Welsby, B. Phillips-Bute, T. L. Ortel, G. M. Arepally, High incidence of antibodies to protamine and protamine/heparin complexes in patients undergoing cardiopulmonary bypass. Blood 121, 2828-2835 (2013).
23. A. Singla, M. J. Sullivan, G. Lee, J. Bartholomew, S. Kapadia, R. H. Aster, B. R. Curtis, Protamineinduced immune thrombocytopenia. Transfusion 53, 2158-2163 (2013).
24. J. J. Van Veen, R. M. Maclean, K. K. Hampton, S. Laidlaw, S. Kitchen, P. Toth, M. Makris, Protamine reversal of low molecular weight heparin: Clinically effective? Blood Coagul. Fibrinolysis 22, 565-570 (2011).
25. J. I. Weitz, J. Hirsh, M. M. Samama; American College of Chest Physicians, New antithrombotic drugs: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 133, 234S-256S (2008).
26. B. P. Schick, D. Maslow, A. Moshinski, J. D. San Antonio, Novel concatameric heparinbinding peptides reverse heparin and low-molecular-weight heparin anticoagulant activities in patient plasma in vitro and in rats in vivo. Blood 103, 1356-1363 (2004).
27. A. C. Rodrigo, A. Barnard, J. Cooper, D. K. Smith, Self-assembling ligands for multivalent nanoscale heparin binding. Angew. Chem. Int. Ed. Engl. 50, 4675-4679 (2011).
28. S. Choi, D. J. Clements, V. Pophristic, I. Ivanov, S. Vemparala, J. S. Bennett, M. L. Klein, J. D. Winkler, W. F. DeGrado, The design and evaluation of heparin-binding foldamers. Angew. Chem. Int. Ed. Engl. 44, 6685-6689 (2005).
29. K. Kaminski, M. Plonka, J. Ciejka, K. Szczubialka, M. Nowakowska, B. Lorkowska, R. Korbut, R. Lach, Cationic derivatives of dextran and hydroxypropylcellulose as novel potential heparin antagonists. J. Med. Chem. 54, 6586-6596 (2011).
30. E. Moreau, M. Domurado, P. Chapon, M. Vert, D. Domurad, Biocompatibility of polycations: In vitro agglutination and lysis of red blood cells and in vivo toxicity. J. Drug Target. 10, 161-173 (2002).
31. T. A. Mixon, G. J. Dehmer, Recombinant platelet factor 4 for heparin neutralization. Semin. Thromb. Hemost. 30, 369-377 (2004).
32. R. H. Roberts, D. M. Monroe, G. C. White, The use of recombinant factor VIIa in the treatment of bleeding disorders. Blood 104, 3858-3864 (2004).
33. E. P. Bianchini, J. Fazavana, V. Picard, D. Borgel, Development of a recombinant antithrombin variant as a potent antidote to fondaparinux and other heparin derivatives. Blood 117, 2054-2060 (2011).
34. G. Lu, F. R. DeGuzman, S. J. Hollenbach, M. J. Karbarz, A. Abe, G. Lee, P. Luan, A. Hutchaleelaha, M. Inagaki, P. B. Conley, D. R. Phillips, U. Sinha, A specific antidote for reversal of anticoagulation by direct and indirect inhibitors of coagulation factor Xa. Nat. Med. 19, 446-451 (2013).
35. W. R. Bukata, Recombinant factor VIIa is effective, but is it cost-effective? Emerg. Med. News 27, 6-10 (2005).
36. J. L. Howes, R. S. Smith, S. D. Helmer, S. M. Taylor, Complications of recombinant activated human coagulation factor VII. Am. J. Surg. 198, 895-899 (2009).
37. G. R. Jones, R. Hashim, D. M. Power, A comparison of the strength of binding of antithrombin III, protamine and poly (L-lysine) to heparin samples of different anticoagulant activities. Biochim. Biophys. Acta 883, 69-76 (1986).
38. M. Imran Ul-haq, B. F. L. Lai, R. Chapanian, J. N. Kizhakkedathu, Influence of architecture of high molecular weight linear and branched polyglycerols on their biocompatibility and biodistribution. Biomaterials 33, 9135-9147 (2012).
39. J. N. Kizhakkedathu, A. L. Creagh, R. A. Shenoi, N. A. Rossi, D. E. Brooks, T. Chan, J. Lam, S. R. Dandepally, C. A. Haynes, High molecular weight polyglycerol-based multivalent mannose conjugates. Biomacromolecules 11, 2567-2575 (2010).
40. T. S. G. Olsson, J. E. Ladbury, W. R. Pitt, M. A. Williams, Extent of enthalpy-entropy compensation in protein-ligand interactions. Protein Sci. 20, 1607-1618 (2011).
41. G. Agnelli, D. J. George, A. K. Kakkar, W. Fisher, M. R. Lassen, P. Mismetti, P. Mouret, U. Chaudhari, F. Lawson, A. G. Turpie; SAVE-ONCO Investigators, Semuloparin for thromboprophylaxis in patients receiving chemotherapy for cancer. N. Engl. J. Med. 366, 601-609 (2012).
42. H. C. Hemker, P. Giesen, R. Al Dieri, V. Regnault, E. De Smedt, R. Wagenvoord, T. Lecompte, S. Béguin, Calibrated automated thrombin generation measurement in clotting plasma. Pathophysiol. Haemost. Thromb. 33, 4-15 (2003).
43. D. Bollinger, M. D. Seeberger, K. A. Tanaka, Principles and practice of thromboelastography in clinical coagulation management and transfusion practice. Transf. Med. Rev. 26, 1-13 (2012).
44. 125I-labelled polyamidoamine dendrimers in vivo. J. Control. Release 65, 133-148 (2000).
45. M. E. Fox, F. C. Szoka, J. M. J. Fréchet, Soluble polymer carriers for the treatment of cancer: The importance of molecular architecture. Acc. Chem. Res. 42, 1141-1151 (2009).
46. P. Bruins, H. Te Velthuis, A. J. Eerenberg-Belmer, A. P. Yazdanbakhsh, E. M. De Beaumont, L. Eijsman, A. Trouwborst, C. E. Hack, Heparin-protamine complexes and C-reactive protein induce activation of the classical complement pathway: Studies in patients undergoing cardiac surgery and in vitro. Thromb. Haemost. 84, 237-243 (2000).
47. S. L. Chudasama, B. Espinasse, F. Hwang, R. Qi, M. Joglekar, G. Afonina, M. R. Wiesner, I. J. Welsby, T. L. Ortel, G. M. Arepally, Heparin modifies the immunogenicity of positively charged proteins. Blood 116, 6046-6053 (2010).
48. S. T. Olson, I. Björk, R. Sheffer, P. A. Craig, J. D. Shore, J. Choay, Role of the antithrombinbinding pentasaccharide in heparin acceleration of antithrombin-proteinase reactions. Resolution of the antithrombin conformational change contribution to heparin rate enhancement. J. Biol. Chem. 267, 12528-12538 (1992).
49. D. H. Atha, J. Lormeau, M. Petitou, R. D. Rosenberg, J. Choay, Contribution of 3-O- and 6-O-sulfated glucosamine residues in the heparin-induced conformational change in antithrombin III. Biochemistry 26, 6454-6461 (1987).
50. L. Berry, A. Stafford, J. Fredenburgh, H. O'Brodovich, L. Mitchell, J. Weitz, M. Andrew, A. K. C. Chan, Investigation of the anticoagulant mechanisms of a covalent antithrombin-heparin complex. J. Biol. Chem. 273, 34730-34736 (1998).
51. M. De Kort, R. C. Buijsman, C. A. Van Boeckel, Synthetic heparin derivatives as new anticoagulant drugs. Drug Discov. Today 10, 769-779 (2005).
52. E. Kizilay, A. B. Kayitmazer, P. L. Dubin, Complexation and coacervation of polyelectrolytes with oppositely charged colloids. Adv. Colloid Interface Sci. 167, 24-37 (2011).
53. J. Van Der Gucht, E. Spruijt, M. Lemmers, M. A. C. Stuart, Polyelectrolyte complexes: Bulk phases and colloidal systems. J. Colloid Interface Sci. 361, 407-422 (2011).
54. S. Reagan-Shaw, M. Nihal, N. Ahmad, Dose translation from animal to human studies revisited. FASEB J. 22, 659-661 (2008).
55. J. Lee, J. W. Sohn, Y. Zhang, K. W. Leong, D. Pisetsky, B. A. Sullenger, Nucleic acid-binding polymers as anti-inflammatory agents. Proc. Natl. Acad. Sci. U. S. A. 108, 14055-14060 (2011).
56. S. A. Smith, S. H. Choi, J. N. Collins, R. J. Travers, B. C. Cooley, J. H. Morrissey, Inhibition of polyphosphate as a novel strategy for preventing thrombosis and inflammation. Blood 120, 5103-5110 (2012).
57. R. J. Travers, R. A. Shenoi, M. T. Kalathottukaren, J. N. Kizhakkedathu, J. H. Morrissey, Nontoxic polyphosphate inhibitors reduce thrombosis while sparing hemostasis. Blood (2014).
58. K. Y. Cho, C. Kim, J. Lee, J. Park, Synthesis and characterization of poly (ethylene glycol) grafted poly (L-lactide). Macromol. Rapid Commun. 20, 598-601 (1999).
59. K. Motogami, M. Kono, S. Mori, M. Watanabe, N. Ogata, A new polymer electrolyte based on polyglycidylether. Electrochim. Acta 37, 1725-1727 (1992).